We seek to be a participating clinical center (PCC) in the RFA entitled "Polycystic Kidney Disease Clinical Trials Network." Hypertension is common, occurs early, and is associated with a faster progression to renal failure in ADPKD. We have shown activation of the systemic renin-angiotensin-aldosterone system (RAAS) in hypertension associated with ADPKD prior to loss of renal function, and that intrarenal activation of RAAS is present. We have demonstrated that angiotensin converting enzyme inhibition alone (ACEI) has beneficial effects by reducing proteinuria and regression of left ventricular hypertrophy as well as improving effective renal plasma flow, and this may relate to filtration fraction. In contrast to other kidney diseases, ACEI has not been as successful in preventing loss of renal function. This may relate to study design issues, sample size, inclusion of low risk individuals not progressing, and less than maximal blockade of RAAS. Therefore, we propose to assess the effect of combination therapy, i.e. ACEI, angiotensin receptor blockade (ARB), and aldosterone antagonism (spironolactone) in the setting of rigorous blood pressure control (<125/75 mm Hg) on the rate of loss of renal function in ADPKD while controlling for other potential contributors to loss of renal function. ADPKD children with hypertension demonstrate a greater increase in renal volume than other ADPKD children in the setting of normal renal function. Using MRI, we have shown decreased renal blood flow in ADPKD as compared to age and gender-matched children suggesting that activation of RAAS occurs early in ADPKD children. We propose to study a special population of ADPKD subjects (children) throughout adolescence to determine the safety and efficacy of ACE/ARB combination therapy in the acute and chronic setting on renal blood flow, and the rate of renal cyst and total renal growth. Taken together, these studies will determine if maximal inhibition of RAAS prevents loss of renal function in ADPKD adults and if combination ACEI/ARB therapy maintains renal blood flow while slowing renal and cyst growth in ADPKD children. Ultimately these studies should demonstrate slowing or halting progression of ADPKD.